Certain therapeutic and bioactive substances, including, but not limited to, (i) medicines, drugs, enzymes, proteins, hormones, and vaccines, (ii) vitamins, minerals, micronutrients and other dietary supplements, (iii) probiotics and other micro-organisms, (iv) cells, cell parts, and/or biological materials, and (v) many other bioactive substances have been found to be vital, therapeutic and necessary for, among other things, the treatment, prevention, and/or inhibition of certain diseases and/or other conditions in humans and animals, the elimination or reduction of pain associated with a wide variety illnesses, diseases and conditions, and/or the general maintenance of good health and well-being in humans and animals, including pets and livestock. For many of these substances, the simplest and most cost-effective method for delivering the medicine or other substance to humans and animals is by oral delivery in the form of a pill, capsule, liquid, paste, or other currently available oral delivery method.
Current oral delivery methods, however, suffer from a number of significant drawbacks and limitations, depending on the substance being delivered. Chief among these is the fact that many substances taken orally are attacked, degraded and/or destroyed in the stomach by stomach acids and/or enzymatic action. This problem would benefit greatly from a viable and cost-effective oral delivery solution.
Even if a substance is not completely destroyed in the stomach by stomach acids and enzymatic action, however, the overall bioavailability and/or therapeutic efficacy of a particular substance, including micro-organisms, can be impacted or greatly reduced by such stomach acids and enzymatic action, depending on the particular substance being orally ingested. Live and active probiotic cultures are one such example. Probiotics are living micro-organisms that naturally reside in the human intestine, and which scientific research has established are vital to a properly functioning immune system, and to our overall physical health and well-being. Through a variety of factors such as disease or the use of antibiotics, the normal balance of “good” versus “bad” bacteria in the intestine can be damaged or seriously impaired, and can even be fatal if left untreated. These imbalances in the microbiome of the intestine have been shown to have other important and vital effects on our health. Many of these imbalances can be, and have been, successfully addressed and treated through the use of live and active probiotic cultures.
In this regard, the US Food and Drug Administration (FDA) and World Health Organization in 2002 recommended that “the minimum viable numbers of each probiotic strain at the end of the shelf-life” be reported on labeling. However, most companies that give a number report the viable cell count at the date of manufacture, a number probably much higher than that which exists at the moment of consumption. Because of variability in storage conditions and amount of time that has elapsed before consuming probiotics, it is difficult to tell exactly how much live and active culture remains at the time of consumption. Due to these ambiguities, the European Commission placed a ban on putting the word “probiotic” on the packaging of such products because such labeling can be misleading.
As a result, most probiotics are either not alive when they are taken orally (and are therefore completely ineffective for recolonizing the gut with “good” or healthy bacteria), or if alive when taken, are often destroyed in the stomach by stomach acids and enzymatic action, leaving a relatively small amount, if any, of the probiotics that actually make it to the small intestine alive and intact, where they are then able to recolonize the gut with the “good” bacteria, or address certain flora deficiencies as needed. As a result of this problem, patients suffering from a Clostridium difficile infection (CDI), for example, must often resort to fecal microbiota transplants (FMT), in order to restore the colonic microflora by introducing healthy bacterial flora directly into the large intestine.
An easier and more cost-effective method of delivering sufficient numbers of live and active probiotic cultures into the small intestine by oral delivery would clearly be a substantial improvement over fecal transplants. In addition, oral delivery of sufficient numbers of live and active probiotics to treat lesser conditions and for the general maintenance of the gut microbiome, with its attendant health benefits, would constitute a significant improvement over current oral delivery methods, which can be inefficient and largely ineffective.
Another problem with many drugs, medicines and other bioactive and therapeutic substances currently administered orally is that oral ingestion of these substances can cause severe stomach upset, nausea, and/or vomiting. These adverse effects are well-known and well-documented, and often appear on the warning label for the medicine as potential side effects. Common aspirin, for example, many prescription pain medications, and many chemotherapy drugs and other medications can, and often do, cause severe stomach upset, nausea, and/or vomiting when taken orally. Millions of people around the world suffer daily from these negative and unpleasant side effects when taking various medications, and so a viable, cost-effective solution is needed and would be a welcome relief to millions of people.
As one example, popular and widely used prescription pain relief medications, many of which are comprised of opioid derivatives such as oxycodone, hydrocodone, codeine, morphine, fentanyl and others, cause stomach upset, nausea, and/or vomiting. These opioid-derived pain medications interact with opioid receptors in the brain and nervous system in order to relieve pain. There were about 300 million pain medication prescriptions written in 2016.
There are two major problems with prescription opioid-based and other pain medications. Number one, they cause stomach upset, nausea, and/or vomiting in a large number of people who take them as previously mentioned. Number two, they are routinely crushed into a powder by drug dealers, and sold to addicts and others who inhale, snort or smoke the powder, or liquify it and inject it directly into their veins or arteries. As a result of this fact, the U.S. is in the midst of a massive opioid epidemic that has been widely reported on and discussed in the media. It is estimated that in 2015 more than 33,000 people died from overdoses of prescription pain medications in the U.S. Annually, opioids kill more people than car accidents and guns, and are now the leading cause of accidental deaths in the U.S.
It would be highly desirable and beneficial to be able to (i) administer pain and other medications orally without encountering any of the negative side effects commonly associated with taking such medications orally (upset stomach, nausea, and vomiting), and (ii) increase the bioavailability and thereby the efficiency of the pain medication, thereby reducing the amount of the pain medication (or dose) required, and (iii) create an oral delivery method which prevents opioid-based pain medications from being concentrated or crushed into a powdered form for use by drug addicts and black market sellers, or makes it prohibitively difficult or expensive to do so.
In the case of the administering medicines and other bioactive and therapeutic substances orally to animals, including pets and livestock, there is the additional problem that many medicines and other bioactive substances do not taste good to the animal, and therefore the animal will refuse to take or eat the medicine or other substance, or will spit out all or a portion of the medicine or other bioactive substance, making it difficult to administer these therapeutic substances to animals. This also results in not knowing exactly how much medicine the animal has taken or ingested, and therefore creates uncertainty as to how effective the unknown dose taken will actually be. The oral administration of medicines and other bioactive substances to animals can also create unnecessary anxiety and trust issues between the animal and the person administering the medicine or other therapeutic substance, and bites and other injuries to persons administering such oral medications and other substances to animals have frequently occurred. This process can also result in the substantial additional expense of having to hire and use a veterinarian or other trained professional to successfully administer the medicine to the animal by injection or other means. Given the widespread nature of these problems, a viable and cost-effective solution would be beneficial and welcome.
Certain vitamins and other dietary supplements are essential to our health and well-being, and evidence-based clinical research supports their importance and wide-ranging health benefits. Among them are Vitamin D, Coenzyme Q10, and Omega-3 fatty acids (EPA/DHA). Omega-3 fatty acids are often sold in the form of fish or Krill oil, or are sold as supplements in a variety of forms. As a result of the established health benefits of these and other vitamins and dietary supplements, they are often recommended or prescribed by physicians. Evidence-based clinical research also strongly suggests these and other dietary supplements should be incorporated into many diets to ensure that sufficient amounts of these critical substances are available for our overall health and well-being.
With respect to omega-3 fatty acids, for example, research has shown that cultures that routinely eat foods with high levels of omega-3 fatty acids demonstrate a variety of health benefits, such as lower levels of depression. Omega-3 fatty acids may also aid in treating the depressive symptoms of bipolar disorder, and may be important for visual and neurological development in infants. When ingested in relatively high doses, it may lower inflammation, which may be important in treating asthma. Other research suggests omega-3 fatty acids may be useful in ameliorating and/or reducing symptoms associated with ADHD in some children, while at the same time enhancing their mental skills. Omega-3 fatty acids may also prove to be useful in the treatment or slowing the progression of Alzheimer's disease and dementia.
With respect to Vitamin D, research has shown it can be important in reducing inflammation (by acting on C-Reactive Protein). It is also thought to aid in reducing pain as well as the stress on joints. Vitamin D has also been implicated as a possible source of reducing rheumatoid arthritis, obesity, certain cancers, various heart diseases, and the effects of radiation, while enhancing individuals' mental capacity, the immune system, bone growth, and the proper production of insulin. Although vitamin D can be procured by exposure to sunlight and other ways, vitamin D can also be attained by oral administration in a supplement form.
With respect to Coenzyme Q10, it is a substance that helps convert food into energy, is found in almost every cell in the body and it is a powerful antioxidant. It is also critical in fulfilling the energy requirements of different organs such as the liver, heart and kidney. It is soluble in oil and present in most eukaryotic cells such as mitochondria. CoQ10 is involved in the electron transport chain and participates in aerobic cellular respiration which generates energy. Over ninety percent of the human body's energy is generated this way. CoQ10 is widely used in numerous applications as an antioxidant. There is also increasing use of CoQ10 in medical applications like heart disease, eye care, cancer treatment, obesity and Huntington's disease.
These and other oil-based dietary supplements, however, face the industry-wide problem of oxidation, which results in the formation of toxic peroxides and other undesirable substances. This oxidation results in degradation of the substance, spoliation, and often a foul and offensive smelling odor and bad breath, all of which can be a strong disincentive for purchasing or taking these supplements again. As a result, dietary supplements such as omega-3 fatty acids, CoQ10 and vitamin D are hampered by oxidation in storage, as well as by the intrinsic properties of the digestive tract, especially the pH differential along the digestive tract. The variable pH from the stomach to the intestine impacts the stability of the substance, and thereby the bioavailability of fat and peptide-based dietary supplements and other bioactive substances. Thus, the bioavailability of these and other dietary supplements are hampered by oxidation in storage, and by the digestive process in the stomach when taken orally.
As a result of these and other problems associated with the oral administration of various bioactive substances, it would be highly desirable and beneficial to have a method of orally delivering these substances to humans and animals, which increases bioavailability and, at the same time, eliminates many of the problems associated with the current oral delivery of these bioactive substances, some of which were discussed above.